Multiwalled Carbon Nanotubes for Combination Therapy: a Biodistribution and Efficacy Pilot Study

A drug delivery system (DDS) for combined therapy, based on a short oxidized multiwalled carbon nanotube, is reported. It was prepared exploiting a synthetic approach which allowed loading of two drugs, doxorubicin and metformin, the targeting agent biotin and a radiolabeling tag, to enable labeling...

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Bibliographic Details
Published in:Journal of materials chemistry. B, Materials for biology and medicine Materials for biology and medicine, 2019-04, Vol.7 (16), p.2678-2687
Main Authors: Biagiotti, Giacomo, Pisaneschi, Federica, Gammon, Seth T, Machetti, Fabrizio, Ligi, Maria Cristina, Giambastiani, Giuliano, Tuci, Giulia, Powell, Emily, Piwnica-Worms, Helen, Pranzini, Erica, Paoli, Paolo, Cicchi, Stefano, Piwnica-Worms, David
Format: Article
Language:English
Subjects:
Animals
Biotin
Breast cancer
Carbon
Cell Line, Tumor
Cell Survival - drug effects
Copper Radioisotopes - chemistry
Doxorubicin
Doxorubicin - chemistry
Doxorubicin - pharmacokinetics
Doxorubicin - pharmacology
Drug Carriers - chemical synthesis
Drug Carriers - chemistry
Drug delivery
Drug delivery systems
Gallium Radioisotopes - chemistry
Isotope Labeling
Metformin
Metformin - chemistry
Metformin - pharmacokinetics
Metformin - pharmacology
Mice
Multi wall carbon nanotubes
Nanotechnology
Nanotubes
Nanotubes, Carbon - chemistry
Pilot Projects
Positron Emission Tomography Computed Tomography
Radiolabelling
Therapy
Tissue Distribution
Toxicity
Tumors
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Summary:A drug delivery system (DDS) for combined therapy, based on a short oxidized multiwalled carbon nanotube, is reported. It was prepared exploiting a synthetic approach which allowed loading of two drugs, doxorubicin and metformin, the targeting agent biotin and a radiolabeling tag, to enable labeling with Ga-68 or Cu-64 in order to perform an extensive biodistribution study by PET/CT. The DDS biodistribution profile changes with different administration methods. Once administered at therapeutic doses, the DDS showed a marginal beneficial effect on 4T1 tumor bearing mice, a syngeneic and orthotopic model of triple negative breast cancer, with survival extended by 1 week and 2 days in 20% of the mice. This is encouraging given the aggressiveness of the 4T1 tumor. Furthermore our DDS was well tolerated, ruling out concerns regarding the toxicity of carbon nanotubes.
ISSN:2050-750X
2050-7518
DOI:10.1039/c8tb03299h